This section is intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention, which are described and/or claimed below. This discussion is believed to be helpful in providing the reader with background information to facilitate a better understanding of various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this light, and not as admissions of prior art.
Many psychological and psychiatric conditions (some of which can be severe and debilitating) affect individuals. These conditions include depression, anxiety disorders, and fatigue. Depression is a mental disorder characterized by episodes of all-encompassing low mood accompanied by low self-esteem and loss of interest or pleasure in normally enjoyable activities. The term “depression” may denote this syndrome, but may refer to other mood disorders or to lower mood states lacking clinical significance. Major depressive disorder is a clinically-diagnosed and disabling condition that adversely affects a person's family, work, and/or school life, sleeping and eating habits, general health, and can lead to self-harm.
Presently, individuals suffering from depression are often treated with antidepressant medication. The treatment of depression was revolutionized in the 1950s by the discovery of monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). This was followed in the 1980s by the advent of the first selective serotonin reuptake inhibitor (SSRI).
Many antidepressant medications work via mechanisms that ultimately increase the amount and availability of neurotransmitters for signaling between nerve cells. In the brain, messages are passed between two nerve cells via a chemical synapse, a small gap between the cells. The presynaptic cell releases neurotransmitters (e.g., serotonin, norepinephrine, etc.) into the synapse. The neurotransmitters are then recognized by receptors on the surface of the postsynaptic cell (i.e., the recipient cell). Following the completion of this process, the large majority of the neurotransmitters are released from the receptors and taken up by monoamine transporters into the presynaptic cell (a process called reuptake). MAOIs, TCAs, and SSRIs function by influencing this process.
As is known to those of ordinary skill in the art, MAOIs are chemicals which inhibit the activity of the monoamine oxidase enzyme family, thus preventing the breakdown of monoamine neurotransmitters and increasing their availability. In the past, MAOIs were prescribed for those resistant to tricyclic antidepressant therapy. However, because of potentially problematic dietary and drug interactions, MAOIs have historically been used only when other classes of antidepressant drugs (e.g., selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.
Tricyclic antidepressants (TCAs) are heterocyclic chemical compounds, the majority of which act primarily as serotonin-norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter and the norepinephrine (NE) transporter, respectively. This results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission.
In recent times, TCAs have been largely replaced in clinical use by newer antidepressants such as the selective serotonin reuptake inhibitors (SSRIs), which typically have more favorable side-effects profiles.
Selective serotonin re-uptake inhibitors (SSRIs)—such as Prozac®, Zoloft®, and Paxil®—are a class of compounds that increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. As a result, the serotonin stays in the synaptic gap longer than it normally would, and may repeatedly stimulate the receptors of the recipient cell.
Apart from MAOIs, TCAs, and SSRIs, additional antidepressant medications have been developed. However, since the advent of SSRIs in the 1980s, newer medications are largely “me too” drugs that exert their primary biochemical effects by increasing the intra-synaptic levels of monoamines.
Typically medications such as MAOIs, TCAs, and SSRIs take weeks to achieve their full effects. For example, high serotonin levels (due to the effects of some antidepressant medications, such as SSRIs) will not only activate the postsynaptic receptors, but also presynaptic autoreceptors, which serve as a feedback sensor for the cell. Activation of the autoreceptors (by agonists like serotonin) triggers a reduction of serotonin production. The resulting serotonin deficiency persists for some time, although the body gradually adapts to this situation by lowering the sensitivity of the autoreceptors.
These slow neurophysiological adaptations of the brain tissue are the reason why several weeks of continuous SSRI use is generally necessary for the antidepressant effect to become fully manifested, and why increased anxiety is a common side effect in the first few days or weeks of use.
Unfortunately, during this lag time, patients continue to suffer from symptoms of depression. Indeed, this lag period in onset of action of traditional antidepressants (of up to several weeks) results in risk of self-harm as well as harm to the patients' personal and professional lives, especially in the first days after starting antidepressant treatment. Furthermore not all patients respond to drugs that increase the intra-synaptic levels of monoamines (such as serotonin).